Nitrate and iodide esters of 5-nitro-2-furfuryl alcohol and preparation of the iodide



a r Sim Para FURFURYL ALCOHOL AND PREPARATION OF THE IODIDE Gabriel Gever, Oxford, N.Y., assignor to The Norwich Pharmacal Company, Norwich, N.Y., a corporation of New York No Drawing. Filed June 30, 1 958, Ser. No. 745,247 2 Claims. (Cl. 260-346.1

This invention relates to a pair of new chemical compounds which are valuable antiseptic and disinfecting agents, one of which is a superior intermediate for the production of the other. My new compounds are the nitrate and iodide esters of 5-nitro-2-furfury1 alcohol and may be represented by the formula:

OnNUCHzX in which X represents a member of the group consisting of I and -ONO radicals.

I have discovered that each of my new compounds possesses an extremely broad antimicrobial spectrum; Each, in small amounts, is inimical to bacteria, fungi and protozoa. Their broad spectrum activity in low concentrations makes them valuable agents as disinfectants and in the preparation of compositions useful in the treatment 30 of superficial infections. They are also valuable in im: parting protection to organic material against attack by microorganisms. v o 7 p The scope of activity of my new compounds is indicated in the following tables setting forth the results of tests to which they were respectively subjected in accordance with accepted procedures:

TABLE I 5-nitro-2-furfuryl nitrate Minimnm'lnhibitory (Joneentration (mg. percent) Species ice 1 2 When tested against E. histolytica, T. vaginalis and T. foetus, complete inhibition of growth was obtained by concentrations as low as about 1 part-of 5-nitro-2-furfuryl nitrate to about 1.25 to 15x10 parts of medium.

TABLE III 5-;iitr0-2-furfuryl iodide Gone. Zones of inhibition in mm. 111mg. 6'. bicans Compound Per! h cent [2Daysr 4Days B Days 8Days' 5.1 25 17 17 17 5-Nttr0-2-iurturyl iodide 2. 0 18 12 12 12 1.0 12 10 9 9 TABLE IV 5-nitr0-2-furfuryl iodide Zones of inhibition Gone. in in mm. (14 days) .Qompound mgpercent A. niger 'lric h.

V v 25 5-Nitro-2-turfuryl iodide 1 10 .25 Control TABLEV S-nitm-Z-furfuryl iodide e v.Conc. Zones of lnhibitionln Compound in mg. mm.M. cam:

' Dcrcent 4 Days 6 Days 8 Days 5-Nitro-2- furfuryl iodide 20 so 44 34} mi 45 :Lscherichia cnli 2-5 q 7 s typj 7 a Wh1,le my new compounds are bothnoteworthy for Qgfgijgjlfifl 14. 1 their broad spectrum" of antimicrobial activity at small Brucella abortus concentrations, they differ from each other inpaiticulars that may be put to advantage in the case of a particular TABLE II 5-nitr0-2-furfuryl nitrate Zones of inhibition in mm.

Oonci, I 7 Species mg. Ag r Agaf+sfirumw Per- 7 cent- 2 4 6 8 2 4 6 8 Days Days Days Days Days Days Days Days C. albicans g 5 31.8 71" M-cama 3,1 25; 18;); T. mentaqrophytea gag 3 E. floccosum 31.8 63 3.18 47 25 T. violaceum 3 1g T. tonsuram .g M. audouini C=c0mp1ete inhibition.

end use. For instance, when an aqueous solution for disinfectant and antiseptic use is desired, I prefer to use 5-nitro-2 furfuryl nitrate as its solubility in water is about 1500 mg./ 1. and aqueous solutions thereof can be prepared very easily. However, when it is desired to confer resistance to fungal attack upon an insulating coating for cables or wires which is composed of-a vinyl plastic derived from 'vinyl'chloride or vinyl esters, or a combination thereof, 5-nitro-2-furfuryl iodide is preferred as an efiective quantity; of that compound (about 0.4% by weight) does not impart an off color to the plastic, nor does it adversely affect its dielectric'properties, and it is resistant to leaching.

. My compoundsmay be readily formulated'with available pharmaceutical excipients in'the form of powders, solutions, suppositories, tinctures, jellies and the like. The following examples are given by way of illustration:

about 0-50 (3., the reaction mixture maintained at a temperature of about 30-50 C. for a brief time period, then cooled and neutralized.

I have further discovered that 5-nitro-2-furfuryl nitrate is an excellent intermediate for the preparation of 5-nitro'-2-furfuryl iodide. In accordance with the practice of this invention, '5-nitro-2-furfuryl nitrate can. be converted to the iodide in a very simple manner, as it is merely necessary to bring the nitrate and sodium iodide together in the presence of acetone whereuponthey will react. The inorganic salt formed inthe reaction precipitates and can be removed by filtration. The 5-nitro-2-furfuryl iodide is then recovered from the filtrate.

Parts In order thatmy invention may be fully available to those skilled in the art, the following examples are given:

Example I 3; 12-15 minutes. The mixture is heated to 40 C. for one Suppository:

a Polyethylene glyco1,(mol. wt. 1,000),. ,84.0%. Polyoxyethylene palniitate 15.9 S-nitro-Z-furfuryl iodide 0.1

Powder:

Talc H 50% Cornstarch 25 Polyoxyethylene glycol (mol. wt. 6000) 24.8 5-nitro-2-furfuryl iodide 0.2

Tincturer Ethyl alcohol 50.00%v 5-nitro- 2 -furfuryl nitrate 0.01 a Water, q.s. 100.00..

Ointment: 7 7

suppository: 7 V Carbowax 1000 '80.'00% 1 Palmitic .acid polyoxyethylene derivative containing 20 oxyethylene units per mol. 19.95 5-nitro-2-furfury1 nitrate 0.05

lly: v Methylcellulose one- 3.0% Glycerine 10.0 Water U I 86.9. S-nitro-Z-fuffuryl nitrate 0.1

Solution: n I

.I, .f5-nitro 2-furfuryl' nitrate.v I 0.01

he toxicity of members of series is iiiivlilbiv'. In mice the LD is about 650-670 mg./kg. Applied to hour, cooled to 25 C. and 1000 cc. of water and 300 grams of trisodium phosphate added. The temperature is raised to C. for one hour; cooled to 10-15FC. and the solid which separates is filtered. The yield of S-nitro- 2 iurfuryl nitrate is 88 gins. (42%); M.P. 36.5 C.

Analysis 0 H N the shaved skin and to the conjunctiva of rabbits. as ,cr n,1;v positions in accordance with the aforesaid examples, no p undue irritation or manifestation of toxicity has beennoted.

My new compounds may be readily and economically,

prepared: 5-nitro-2-furfuryl nitrate can be prepared in high yield and pure form by nitrating the common, m-

- finitely water-soluble form of furfuryl alcohol.-In-ac-.

the alcohol cordance with the practice of this invention,

is treated with a nitrating agent, such as one composed of Example 11 jj 'A solution of 300 g. (2 moles) of sodium iodide in one liter of acetone in a three-liter Erlenmeyer flask is treated with a solution of 375 g. (1.995 moles) of 5- nitro-2-furfuryl nitrate in 500 ml. acetone and cooled,

overnight in the refrigerator. The precipitated sodium nitrate is removed by filtration and is washed with 300 ml. acetone and dried to 163 g. (theory, g.). The filtrate is combined with the acetone washings and diluted with ten liters of water. The separated oil crystallizes after the mixture is stirred for an hour. The yield of crude 5-nitro-2- furfuryl iodide after being air dried is 500 g. (theory 506 g.). The crude material is recrystallized from three liters of isopropyl alcohol anddecolon ized with charcoaLfThe product separates as an oil, which crystallizes'when agitated. This. is .recrystallized from'two liters of'isopropyl alcohol; The hot solution is stirred vigorously for two hours, while being cooled with an ice bath. 326 g. of yellow crystals is recovered, M.P. 58 C., which is a yield of 6 5 0f 5-nitr0-2-furfuryl io ide I What I claim is:

LThe chemical compound S-nitro-Z-furfuryl nitrate. 2. The process of preparing 5-nitro-2-furfuryl iodide which comprises causing 5-nitro-2-furfuryl nitrate to react with sodium iodide by bringing them together in the presence of acetone;

References Cited in thefile of this patent Gilman et al.: Iowa State College, J. Sci., vol. 6 (1932), 

1. THE CHEMICAL COMPOUND 5-NITRO-2-FURFURYL NITRATE. 